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A Study of Oral LBH589 in Adult Patients With Advanced Hematological Malignancies

Primary Purpose

Lymphoma, Leukemia, Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LBH589
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring HDAC inhibitor, Oral, LBH589, Lymphoma, Leukemia, Multiple myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Adult patients (≥18 years old) with advanced hematological malignancies who relapsed after or are refractory to standard therapy, or for which no standard therapy existed; or, were considered inappropriate candidates for standard therapy
  • World Health Organization (WHO) performance status ≤ 2
  • Patients who met protocol-specified hematologic and non-hematologic laboratory values
  • Patients with adequate liver and renal function

Exclusion criteria:

  • Concurrent brain metastases or leukemic infiltration of the cerebrospinal fluid
  • Peripheral neuropathy ≥ CTCAE grade 2
  • Unresolved diarrhea ≥ CTCAE grade 2
  • Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study, including impaired heart function or clinically significant heart disease, and impaired gastrointestinal function or disease that significantly altered aborption of LBH589
  • Female patients who were pregnant or breast feeding
  • Patients who were unwilling to use an effective method of birth control
  • Patients who took medications specified by the protocol as prohibited for administration in combination with LBH589
  • Patients with another primary malignancy that required active intervention or were clinically significant

Sites / Locations

  • Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia
  • Dana Farber Cancer Institute
  • MD Anderson Cancer Center/University of Texas
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm 1, Group X

Arm 1, Group Y

Arm 2, Group X

Arm 2, Group Y

Arm Description

Panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF), every other week, as part of a 28-day treatment cycle. Group Y is a sub-arm, based on disease indication.

Outcomes

Primary Outcome Measures

Number of Participants DLT in Arm 1 in Dose Escalation Phase
Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for consecutive dosing schedule (MWF weekly). A 3-parameter version of a Bayesian logistic regression model with overdose control (Babb, Rogatko, and Zacks 1998) was used during the dose escalation phase for dose level selection and determination of the MTD.
Number of Participants DLT in Arm 2 in Dose Escalation Phase
Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for intermittent dosing schedule (MWF weekly). A 3-parameter version of a Bayesian logistic regression model with overdose control (Babb, Rogatko, and Zacks 1998) was used during the dose escalation phase for dose level selection and determination of the MTD.

Secondary Outcome Measures

Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML)
Response as per investigator assessment for patients include complete response, progressive disease/failure, stable disease.
Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML) in Expansion Phase
Stage 2 did not open for enrollment.
Response as Per Investigator Assessment for Patients With Hodgkin's Lymphoma (HD)
Response as per investigator assessment for patients include complete response, partial remission, stable disease, progressive disease (PD)/failure.
Response as Per Investigator Assessment for Patients With Myelodysplastic Syndromes (MDS)
Response as per investigator assessment for patients include complete response, stable disease, progressive disease/failure, partial remission.
Maximum Plasma Concentration of Panobinostat After the First Dose in Arms 1 and 2
Half Life of Panobinostat After the First Dose in Arms 1 and 2
Maximum Plasma Concentration of Panobinostat After Multiple Doses in Arm 1 on Day 15
From day 15 by dose with schedule: MWF every week
Half Life of Panobinostat After Multiple Doses in Arm 1 on Day 15
Geometric Mean Ratio (GMR) Comparing Treatment Days in Arm 1
MWF Every week schedule n = number of subjects with non-missing values.
Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group X
Reporting the number of patients with a reading at the timepoint in the dose group.
Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group Y
Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group X
Percentage of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group Y
Highest Percent Change in Fetal Hemoglobin From Baseline in Arm 1 (MWF Every Week)
All blood samples were drawn immediately prior to each administration of LBH589 dose and at the end of treatment (≤ 7 days post last dose (preferably ≥ 4 days [96 hours]))
Highest Percent Change of Fetal Hemoglobin From Baseline in Arm 2 (MWF Every Other Week)
All blood samples were drawn immediately prior to each administration of LBH589 dose and at the end of treatment (≤ 7 days post last dose (preferably ≥ 4 days [96 hours]))

Full Information

First Posted
February 12, 2008
Last Updated
December 16, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00621244
Brief Title
A Study of Oral LBH589 in Adult Patients With Advanced Hematological Malignancies
Official Title
A Phase IA/II, Two-arm, Multi-center, Open-label, Dose-escalation Study of LBH589 Administered Orally Via Different Dosing Schedules in Adult Patients With Advanced Hematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
March 1, 2003 (Actual)
Primary Completion Date
December 3, 2009 (Actual)
Study Completion Date
December 3, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This study evaluated safety, tolerability, pharmacokinetics and preliminary anti-leukemic or anti-tumor activity of LBH589B in adult patients with advanced hematological malignancies

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Leukemia, Multiple Myeloma
Keywords
HDAC inhibitor, Oral, LBH589, Lymphoma, Leukemia, Multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
175 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1, Group X
Arm Type
Experimental
Arm Title
Arm 1, Group Y
Arm Type
Experimental
Arm Title
Arm 2, Group X
Arm Type
Experimental
Arm Title
Arm 2, Group Y
Arm Type
Experimental
Arm Description
Panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF), every other week, as part of a 28-day treatment cycle. Group Y is a sub-arm, based on disease indication.
Intervention Type
Drug
Intervention Name(s)
LBH589
Primary Outcome Measure Information:
Title
Number of Participants DLT in Arm 1 in Dose Escalation Phase
Description
Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for consecutive dosing schedule (MWF weekly). A 3-parameter version of a Bayesian logistic regression model with overdose control (Babb, Rogatko, and Zacks 1998) was used during the dose escalation phase for dose level selection and determination of the MTD.
Time Frame
Cycle 1 (28-day treatment cycle)
Title
Number of Participants DLT in Arm 2 in Dose Escalation Phase
Description
Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for intermittent dosing schedule (MWF weekly). A 3-parameter version of a Bayesian logistic regression model with overdose control (Babb, Rogatko, and Zacks 1998) was used during the dose escalation phase for dose level selection and determination of the MTD.
Time Frame
Cycle 1 (28-day treamtent cycle)
Secondary Outcome Measure Information:
Title
Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML)
Description
Response as per investigator assessment for patients include complete response, progressive disease/failure, stable disease.
Time Frame
3.5 years
Title
Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML) in Expansion Phase
Description
Stage 2 did not open for enrollment.
Time Frame
1.2 years
Title
Response as Per Investigator Assessment for Patients With Hodgkin's Lymphoma (HD)
Description
Response as per investigator assessment for patients include complete response, partial remission, stable disease, progressive disease (PD)/failure.
Time Frame
3.5 years
Title
Response as Per Investigator Assessment for Patients With Myelodysplastic Syndromes (MDS)
Description
Response as per investigator assessment for patients include complete response, stable disease, progressive disease/failure, partial remission.
Time Frame
3.5 years
Title
Maximum Plasma Concentration of Panobinostat After the First Dose in Arms 1 and 2
Time Frame
Day 1
Title
Half Life of Panobinostat After the First Dose in Arms 1 and 2
Time Frame
Day 1
Title
Maximum Plasma Concentration of Panobinostat After Multiple Doses in Arm 1 on Day 15
Description
From day 15 by dose with schedule: MWF every week
Time Frame
Day 15
Title
Half Life of Panobinostat After Multiple Doses in Arm 1 on Day 15
Time Frame
Day 15
Title
Geometric Mean Ratio (GMR) Comparing Treatment Days in Arm 1
Description
MWF Every week schedule n = number of subjects with non-missing values.
Time Frame
Day 15/day 1
Title
Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group X
Description
Reporting the number of patients with a reading at the timepoint in the dose group.
Time Frame
Days 1, 5, 8, 10, 15
Title
Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group Y
Time Frame
Days 5, 8, end of study (up to 3.5 years)
Title
Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group X
Time Frame
Days 5, 8, 10, 12, 15, End of study, Unscheduled (up to 3.5 years)
Title
Percentage of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group Y
Time Frame
Days 5, 8, 10, 12, 15, End of study (up to 3.5 years)
Title
Highest Percent Change in Fetal Hemoglobin From Baseline in Arm 1 (MWF Every Week)
Description
All blood samples were drawn immediately prior to each administration of LBH589 dose and at the end of treatment (≤ 7 days post last dose (preferably ≥ 4 days [96 hours]))
Time Frame
Post dose to pre-dose (up to 3.5 years)
Title
Highest Percent Change of Fetal Hemoglobin From Baseline in Arm 2 (MWF Every Other Week)
Description
All blood samples were drawn immediately prior to each administration of LBH589 dose and at the end of treatment (≤ 7 days post last dose (preferably ≥ 4 days [96 hours]))
Time Frame
Post dose to pre-dose (up to 3.5 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Adult patients (≥18 years old) with advanced hematological malignancies who relapsed after or are refractory to standard therapy, or for which no standard therapy existed; or, were considered inappropriate candidates for standard therapy World Health Organization (WHO) performance status ≤ 2 Patients who met protocol-specified hematologic and non-hematologic laboratory values Patients with adequate liver and renal function Exclusion criteria: Concurrent brain metastases or leukemic infiltration of the cerebrospinal fluid Peripheral neuropathy ≥ CTCAE grade 2 Unresolved diarrhea ≥ CTCAE grade 2 Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study, including impaired heart function or clinically significant heart disease, and impaired gastrointestinal function or disease that significantly altered aborption of LBH589 Female patients who were pregnant or breast feeding Patients who were unwilling to use an effective method of birth control Patients who took medications specified by the protocol as prohibited for administration in combination with LBH589 Patients with another primary malignancy that required active intervention or were clinically significant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
MD Anderson Cancer Center/University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
Novartis Investigative Site
City
Prahran
State/Province
Victoria
ZIP/Postal Code
3181
Country
Australia
Facility Name
Novartis Investigative Site
City
Frankfurt/M
ZIP/Postal Code
60590
Country
Germany
Facility Name
Novartis Investigative Site
City
Mainz
ZIP/Postal Code
55131
Country
Germany

12. IPD Sharing Statement

Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=3800
Description
Results for CLBH589B2102 can be found on the Novartis Clinical Trial Results Website

Learn more about this trial

A Study of Oral LBH589 in Adult Patients With Advanced Hematological Malignancies

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